Ionization of non-volatile and thermally unstable biomolecules, as well as many synthetic polymers, is possible by the use of soft ionization techniques like electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI). MALDI in particular is a useful technique and is able to determine the molecular weight of polar to relatively non-polar analytes in a mass range of 300 to over 1,000,000 Da without fragmentation.[1] In contrast to ESI, MALDI produces ions with only one charge, so that the interpretation is facilitated. In addition, ESI ionizes only polar to moderately polar substances, and discrimination effects are frequently observed with compounds of high molecular weight.
The result of a MALDI analysis is highly dependent on the sample preparation. The dried droplet (DD) technique (also known as solvent evaporation technique) is the most commonly used method because it is very easy to carry out.[1] For this purpose, the substances to be analysed and matrix are applied to the target dissolved in a suitable solvent. The solvent then evaporates to leave solid matrix and analyte, which can then be desorbed by action of the MALDI laser. Whilst the DD technique permits rapid sample preparation and is amenable to scaling up (using “target printing” techniques) to form large numbers of samples simultaneously, it has significant drawbacks in terms of sample quality and reproducibility. In particular, solvent evaporation leads to inhomogeneous crystallization, so that chromatographic effects result and lead to a concentration distribution of the analyte on the target.[2] in the case of the analysis of a synthetic polymer, it can even result in a spatial distribution of oligomers within a single sample.[2] Thus under solvent-based conditions reproducible results are difficult to obtain.[2] This prevents widespread industrial use of this otherwise very powerful mass spectrometric method.
Some attempts have been made to address these drawbacks. In particular, it has been suggested that improved homogeneity can be achieved using solvent-free sample preparation techniques. It has been proposed that solvent can be excluded by grinding the solid sample and spreading the resulting powder on a sample plate.[7-10]
A solvent-free method where the solid sample powder is highly compressed into a pellet has also been suggested,[8-10] the compressed pellet is attached to the sample plate by double sided conductive tape.[8] However, the high density of the compressed pellet has been found by the author to hamper desorption.[8] The same authors found that direct powder application shows better resolution and sensitivity than the pressed pellet application.[8-10] It has been suggested that the method of transferring the sample to the MALDI target plate influences sensitivity and mass resolution, saying that employing loose powder transfer, rather than transferring the compressed pellet, improves sensitivity and gives higher mass resolution.[16]